Cell density modulates protein-tyrosine phosphorylation.
The growth of normal cells is arrested at saturating cell density in a process termed contact inhibition. An understanding of how cells communicate their contact with one another is critical for determining how cancers develop and spread. Because the molecular details of how fibroblasts communicate density changes are unclear, we examined cell density itself as a source of signaling events rather than examine specific receptors. A technique was developed to measure tyrosine phosphorylation acutely as a function of cell density. The tyrosine phosphorylation of a number of proteins was found to be modified in response to cell density. Three of these proteins were identified as Src, paxillin, and focal adhesion kinase (FAK), all of which show an increase in their tyrosine phosphate levels with increasing density. All of these proteins are found in focal adhesions, and both FAK and paxillin are believed to be localized exclusively in focal adhesions. Thus, changing cell density alters tyrosine phosphorylation of focal adhesion components.
Batt
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DB
Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Roberts
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TM
D016475:3T3 Cells; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002455:Cell Division; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D008807:Mice, Inbred BALB C; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C496051:Ptk2 protein, mouse; D017027:Protein Tyrosine Phosphatases